Antimicrobials drugs
Dr. Mohammed Al-Khawlani
Assist. Professor of pharmacology and Toxicology
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Introduction of antimicrobials
❑ The term chemotherapy: was chemical substances (drugs) used to kill or stop growth of
infective microbes (Antimicrobials), now drugs to kill cancer cells (anti-cancer chemotherapy).
❖ Chemotherapy includes:
1. Antimicrobial Agents
➢ They include antibacterial, antifungal and antiviral drugs.
➢ Antibiotics: agents derived from living organisms (bacteria, fungi or mold) to be used
to kill or stop growth other microorganisms as Penicillins , cephalosporins ,
tetracyclines, chloramphenicol
➢ They are more selective on microorganisms with less toxic effects in human (Selective
toxicity), depend on the biochemical different between microbe and the host cell.
2. Antiparasitic Agents
➢ Anthelmintics and antiprotozoal drugs.
3. Anticancer Chemotherapy
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Classification of Bacteria
❖ Bacterial structure
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Classification of Bacteria
❖ Classification of Bacteria:
1. According to Pathogenicity
A- Non-pathogenic: as normal flora (Staphylococcus epidermidis, Lactobacillus acidophilus
B- Pathogenic: as Neisseria gonorrhea, Streptococcus pneumoniae.
2. According to Growth Requirement :
A- Aerobics: most of bacteria.
B- Anaerobic: as, clostridium spp.
3. According to Gram Staining :
A- Gram positive (Gm +ve)
B- Gram negative (Gm-ve)
C- Non-Gram Stain bacteria (Atypical bacteria): as Mycoplasma, Chlamydia , Mycobacteria
and Legionella.
4. According to shape of bacteria
- Cocci:
- Bacilli (Rods)
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Classification of Bacteria
Types of pathogenic bacteria
Gram +ve bacteria
Gram +ve cocci Disease Gram+ve bacilli Disease
Staphylococci -Skin infections -Corynobacerium -Diphteria
-Acute endocarditis
*MSSA Surgical wounds
- MRSA -Osteomylitis
*Vancomycin resistant -Diabetic foot
-Urinary tract infections
Streptococci -Upper respiratory tract infections Bacillus anthrax Anthrax
• tonsillitis, pharyngitis, otitis,
sinusitis.
- Lower respiratory tract
infections: bronchitis &
pneumonia
-Sub acute endocarditis
(Rheumatic fever).
Enterococci -Peritonitis. Closterium -food poisoning
-Urinary tract infections botulonimi
-Gastroenteritis Clonstridium tetani -Tetanus
- Endocarditis
Listeria -Meningitis in
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monocytogenes neonates
Classification of Bacteria
Gram –ve bacteria
Gram-ve cocci Disease Gram-ve bacilli Disease
-Neisseria meningitis Meningitis In respiratory tract
-Lower respiratory tract infect.
Niseeria gonorrhea Gonorrhea Hemophilus influenza - Meningitis
Potadella pertussus -Upper respiratory tract infect.
-Moraxella -Upper respiratory tract -In urinary tract infections
infections (URTI) (enterobacilli)
• tonsillitis, -E. coli, kelpsiella , proteus, -Urinary tract infections
pharyngitis, otitis, enterobactrer -Gastroenteritis
Serratia -Aspiration pneumonia
-Conjunctivitis -Neonatal meningitis
Pseudomonas
Pneumococi In small intestine
*Non penicillin producing -Meningitis Vibro cholera -Cholera
*Penicillin producing -Pneumoni -Salmonella typi¶typi -Typhoid fever
-Brucella -Brucellosis
-yersenia -Plague
In large intestine
-shegella & salmonella Gastrointeritis
In stomach& duodenum
Helicobacter pylori -Peptic ulcer
Cambellobacter pylori -Deodenitis
Psudomonas -Urinary tract infections
-Nosocomial infections
-Infections in immuno-
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suppressed persons
Classification of Bacteria
Anaerobes Disease Atypical bacteria Diseases
-Peptidococci -Localized abscess in In genital tract
lung ,brain , root of teeth -Treponema -Syphilis
-Peptidostreptococci , pelvis , genital organs
-Chlamydia - Uro-genital infect.
Pneumonia, Eye infections
(trachoma).
In central nervous
-Clostridium perfingis Gas gangrene system
Rickettsia -Rocky mountain fever
-Borrelia -Lyme diseases
-Clostridum difficle Pseudomembranous In respiratory tract
colitis Nocardia -Nocardiosis
Mycoplasma -Atypical pneumonia
Myobactrium TB -Tuberculosis
-Propriobacterium acne Acne valgais Bones Actinomycosis
G-ve = GIT, UTI, RTI, meningitis G +ve= RTI & skin
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Classification of Bacteria
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Antibacterial drugs
❖ Antibacterial drugs (Antibiotic)
▪ Drugs or chemical substances that used to inhibit the growth or kill bacteria
❖ Classification of antibacterial drugs:
1. According to their source:
A. Natural: from fungi e.g. Penicillin
from bacteria e.g. Gentamycin
B. Semisynthetic: e.g. Ampicillin
.
C. Synthetic: e.g. fluoroquinolones .
2. According to the activity of the drug:
a) Bacteriostatic: stop growth and multiplication of bacteria ( need active immune) e.g.
macrolides & tetracycline.
b) Bactericidal: kill the bacteria (no need active immune) e.g. B-lactam, vancomycin, and
aminoglycosides.
• used in serious infections as endocarditis, septicemia, and meningitis.
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Anti- bacterial drugs
N.B.:
- few antibacterial may be bacteriostatic or bactericidal according to their concentration
or the state of activity of bacteria, e.g. erythromycin and isoniazid.
3. According to the spectrum of activity:
Broad spectrum Narrow spectrum
-Effective against multiple gram +ve & -Effective against specific organisms
Gm -ve organisms
Imipenem , tetracycline, quinolones Antimicrobial against gram +ve bacteria
,chloramphenicol , cotrimoxazole Erythromycin, clindamycin, vancomycin,
bacitracin, daptomycin, streptogramins &
linezolid, Penicillin G
Antimicrobial against gram -ve bacteria:
aminoglycosides ,aztreonam
Used as initial empirical treatment till -Used in treatment of susceptible organisms based
culture ,sensitivity results appear on culture and sensitivity results
Rapid development of resistance Slow development of resistance
-Superinfection with resistant strains -Superinfection with resistant strains and
and, pseudomembranous colitis are pseudomembranous colitis are less common
common
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Antibacterial drugs
3. According to their mechanism of action:
a) Inhibitors of cell wall synthesis: As: B- Lactam, vancomycin, cycloserine.
b) Inhibitors of protein synthesis by:
-Inhibition of 30 S ribosomal subunit As: tetracycline, aminoglycosides
-lnhibition of 50 S ribosomal subunit: As macrolides & Chloramphenicol.
c) Inhibitors of nucleic acid synthesis: As: rifampicin, quinolones.
d) Inhibitors of cell membrane function: As: isoniazid.
e) Inhibitors of folic acid synthesis: As: sulphonamides.
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Anti- bacterial drugs
❖ Antimicrobial Therapy
▪ Empirical therapy: use of antimicrobial agents before identification of causative
organism or availability of susceptibility test results.
- Immediate empiric therapy is indicated in critically ill or serious infections patient until
the result of culture and sensitivity test is revealed.
- Broad-spectrum therapy may be needed initially: e.g. Community-aquired pneumonia
with Macrolid or Fluoroquinolones
▪ Definitive therapy: use of antimicrobial agent after identification / susceptibility tests of
causative organism responsible for the disease.
- Narrow-spectrum therapy may be needed
- The antimicrobial agent should be selected according to the type of organism, culture and
sensitivity reports.
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Antibacterial drugs
❖ Factors affecting Selection of antibacterial agent
❑ Identification of the infecting organism:
❑ Patient factors:
▪ In neonates, the use → toxic effect:
- chloramphenicol → gray baby syndrome .
- Sulfonamides → kernicterus (brain damage)
▪ In growing children, the use of:
- Fluoroquinolones → arthropathy
- Tetracyclines → abnormal teeth and bone formation.
▪ In old age (> 65 years): renal toxicity with
aminoglycosides is greater than in younger patients.
▪ In immunocompromised patients, the use of
bactericidal agents is necessary.
▪ Pregnancy: antibiotics cross the placenta and cause
adverse effects to the fetus e.g. aminoglycosides and
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tetracyclines. FDA categories of antimicrobials and fetal risk
Antibacterial drugs
❑ The site of the infection: Lipid solubility, Molecular weight.
▪ Lipid soluble antibiotics e.g. prostate, and blood–brain barrier
- chloramphenicol and metronidazole can cross the barriers in normal conditions.
- Penicillin: cannot cross the barriers unless inflammation is present.
❑ The safety of the agent: penicillin are among the least toxic, chloramphenicol potential for
serious toxicity
❑ The cost of therapy & route of administration:
- Several drugs may show similar efficacy in treating an infection but vary widely in cost.
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Antibacterial drugs
❖ Frequency Of Antibiotic Dosing
➢ Concentration-dependent killing:
- Bactericidal effect depends on drug concentration (↑ rate of bacterial killing as the
concentration of antibiotic increases)
- Aminoglycosides, Quinolones and daptomycin
- Giving by a single large dose per day → achieves high peak levels and cause rapid killing
of bacteria.
➢ Time-dependent killing:
- Bactericidal effect depends on the percentage of time that the drug concentration in the
blood remains above the MIC.
- β-lactam antibiotics, macrolides, clindamycin, and linezolid
- So, preparations with long duration kill more bacteria.
➢ Post-antibiotic effect (PAE):
- a persistent bacterial suppression after levels of antibiotic fall below the MIC.
- Antimicrobials with long PAE (e.g. aminoglycosides and fluoroquinolones, Erythromycin,
Tetracycline, Clindamycin, Streptogramins, linezolid) often require only one dose per day
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Antibacterial drugs
❖ Combination Therapy
❖ Advantages of drug combinations:
- To achieve synergism. as β-lactams + aminoglycosides
- To reduce the incidence of bacterial resistance. As TB
- To broaden the spectrum. As Amoxicillin + Clavulanic acid.
- To treat mixed infections. Diabetic foot
- To treat serious infections as septicemia.
❖ Disadvantages of drug combinations:
• Bactericidal + bacteriostatic drugs → Antagonism ((cidal drugs act on active growing and
multiplying bacteria, e.g. tetracycline → ↓ penicillin efficacy)
• Development of antibiotic resistance by giving unnecessary combination therapy.
• ↑ risk of superinfection.
1. Static + Static → Addition.
2. Cidal + Cidal → Synergism.
3. Static + Cidal → Antagonism
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Antibacterial drugs
❖ Antibacterial resistance
▪ Antibacterial resistance is the ability of bacteria to grow in the presence of a drug that
would normally kill them or limit their growth.
❑ Mechanism of resistance:
1- Synthesis of inactivating enzymes → destroy antimicrobial agents such as:
- Penicillinase produced by staphylococci, some streptococci , pneumococci , H. influenzas
- Acetyltransferase produced by Gram –ve bacilli → inactivate aminoglycosides and
chloramphenicol by transference of the acetyl group.
2- Inhibition of entry of antibiotics inside the bacterial cells eg
- pseudomonas and other Gm -ve bacilli inhibit the entry of aminoglycosides by loss or
mutation of porins
▪ efflux pump that can transport drugs out of the cell. such as tetracycline
3- Target modification:
▪ Modification of the target site by chromosomal change. As erythromycin and
fluoroquinolones)
▪ Alteration of bacterial penicillin-binding proteins. (Streptococci pneumoniae resistance to
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β-lactam)
Antibacterial drugs
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Antibacterial drugs
❖ Complication of antibacterial therapy:
1. Hypersensitivity (Anaphylactic reaction): Ex. Penicillins
▪ characterized by hypotension, bronchospasm, vascular collapse and may lead to shock..
▪ Treated mainly by adrenalin, hydrocortisone, antihistamines and oxygen.
▪ Test for allergy must be done. (Sensitivity test)
2. Direct toxicity
▪ High serum levels of certain antibiotics as; aminoglycosides may cause ototoxicity
3. Superinfections
▪ Broad-spectrum antimicrobials (as Clindamycin, fluoroquinolone) or combinations of
agents → kill of the normal flora → overgrowth of opportunistic organisms, especially
fungi or resistant bacteria as clostridium difficile → pseudomembranous colitis
(antibiotic-associated diarrhea).
• treatment by: 1- Stop used the antibacterial drugs
2- Metronidazole or Vancomycin orally
3- Antifungal as; nystatin for candidiasis
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